Catalytic RNA May Provide New Treatment for HIV

Dr. John Burke is a professor in the microbiology and molecular genetics department at the University of Vermont, and his research may hold the key to the a new antiviral treatment which would help combat viruses like Hepatitis B and HIV. Dr. Burke has been working with catalytic RNA since the mid-1980’s, and began to investigate its anti-viral properties in the early 90’s.

RNA, ribonucleic acid, is used in cells system of storing information, and is very similar in structure to the primary component of the human genome: DNA. Catalytic RNA is RNA which can perform certain enzymatic functions; for example, some catalytic RNA can act alone to convert itself from a linear conformation to a circular one.

Many scientists have suggested that RNA was the genetic material of the earliest organisms on Earth, since it can both store information and perform chemical reactions without outside intervention. In humans, DNA serves only to store information and cannot carry out essential reactions, and the proteins which carry out those reactions cannot store information.

Dr. Burke’s laboratory on campus has been researching the function of catalytic RNA in general in an attempt to understand it, and has been working towards demonstrating its ant-viral capabilities. Burke’s lab has successfully shown that if the catalytic RNA he works with can enter a virally-infected cell, that RNA will act to damage or destroy the virus.

A major problem in successfully applying this technique is getting the RNA into the target cells: alone, RNA is very unstable and cannot survive for long periods of time outside of cells. There are two major approaches to this: using liposomes, and gene therapy. Liposomes are simply hollow balls of lipid (fat) molecules capable of fusing with cell membranes, thereby injecting their contents into cells. Gene therapy is the process of attempting to physically incorporate RNA into the target cell’s genome.

At first, gene therapy was the preferred path of researchers in the field, and clinical trials had begun to determine its effectiveness. However, in 2002, gene therapeutic techniques being used in France to combat Severe Combined Immunodeficiency (bubble boy syndrome) appeared to be causing cancer in many of the recipients. The reason for this is that scientists cannot precisely control the point in the genome where new DNA or RNA incorporates – this uncertainty can lead to disruption of a gene necessary for normal cell function, and cause cancer.

As a result of the French trials, gene therapy slowed to a crawl across the board, and Dr. Burke’s catalytic RNA project was moved to the back burner. Until researchers can come up with an effective way to get the RNA into the target cells, Burke’s lab will continue to focus primarily on understanding the mechanisms by which catalytic RNA acts